The role of trimethylamine‐N‐Oxide in the development of Alzheimer's disease

Alzheimer's disease is associated with multiple risk factors and is the most common type of dementia. Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite derived from dietary choline and carnitine, has recently been identified as a potential risk factor of Alzheimer's disease. It has been demonstrated that TMAO is associated with Alzheimer's disease through various pathophysiological pathways. As a result of molecular crowding effects, TMAO causes the aggregation of the two proteins, amyloid-beta peptide and tau protein. The aggregation of these proteins is the main pathology associated with Alzheimer's disease. In addition, it has been found that TMAO can activate astrocytes, and inflammatory response. Besides molecular investigation, animal and human studies have also supported the existence of a functional relationship between TMAO and cognitive decline. This article comprehensively summarizes the relationship between TMAO and Alzheimer's disease including emerging evidence from in vitro, in vivo, and clinical studies. We hope that this knowledge will improve the prevention and treatment of Alzheimer's disease in the near future.